Antibacterial oral composition

ABSTRACT

An antibacterial oral composition effective to promote oral hygiene containing an antibacterial antiplaque agent and an additive which reduces straining of dental surfaces without substantially diminishing the antibacterial and antiplaque activity of the agent. Bis-biguanido hexanes, such as chlorhexidine and alexidine, and quaternary ammonium salts, such as benzethonium chloride and cetyl pyridinium chloride, are typical examples of antibacterial agents. The antistain additive is a phosphono polycarboxylic acid compound, such as 1-phosphonoethane-1,2-dicarboxylic acid and salts thereof.

This invention relates to an antibacterial oral composition whichpromotes oral hygiene.

Cationic antibacterial materials are well known in the art. See, forinstance the section on "Quaternary Ammonium and Related Compounds" inthe article on "Antiseptics and Disinfectants" in Kirk-OthmerEncyclopedia of Chemical Technology, 2nd edition (Vol. 2, p. 632-635),incorporated herein by reference. Cationic materials which possessantibacterial activity (i.e. are germicides) are used against bacteriaand have been used in oral compositions to counter plaque formationcaused by bacteria in the oral cavity.

Among the most common of these antibacterial antiplaque quaternaryammonium compounds is benzethonium chloride, also known as Hyamine 1622or diisobutylphenoxyethoxyethyl dimethyl benzyl ammonium chloride. In anoral preparation this material is highly effective in promoting oralhygiene by reducing formation of dental plaque and calculus, which isgenerally accompanied by a reduction in caries formation and periodontaldiseases. Other cationic antibacterial agents of this type are thosementioned, for instance, in U.S. Pat. Nos. 2,984,639, 3,325,402,3,431,208 and 3,703,583, and British Pat. No. 1,319,396.

Other antibacterial antiplaque quaternary ammonium compounds includethose in which one or two of the substituents on the quaternary nitrogenhas a carbon chain length (typically alkyl group) of some 8 to 20,typically 10 to 18, carbon atoms while the remaining substituents have alower number of carbon atoms (typically alkyl or benzyl group), such as1 to 7 carbon atoms, typically methyl or ethyl groups. Dodecyl trimethylammonium bromide, benzyl dimethyl stearyl ammonium chloride, cetylpyridinium chloride and quaternized 5-amino-1,3-bis(2-ethylhexyl)-5-methyl hexa hydro-pyrimidine are typical quaternaryammonium antibacterial agents.

Other types of cationic antibacterial agents which are desirablyincorporated in oral compositions to promote oral hygiene by reducingplaque formation are the amidines such as the substituted guanidinese.g. chlorhexidine and the corresponding compound, alexidine, having2-ethylhexyl groups instead of chlorophenyl groups and otherbis-biguanides such as those described in German patent application P2,332,383 published Jan. 10, 1974, which sets forth the followingformula: ##STR1## in which A and A' signify as the case may be either(1) a phenyl radical, which as substituent can contain up to 2 alkyl oralkoxy groups with 1 up to about 4C-atoms, a nitro group or a halogenatom, (2) an alkyl group which contains 1 to about 12 C-atoms, or (3)alicyclic groups with 4 to about 12C-atoms, X and X' as the case may bemay represent an alkylene radical with 1-3C-atoms, z and z' are as thecase may be either zero or 1, R and R' as the case may be may representeither hydrogen, an alkyl radical with 1 to about 12C-atoms or anaralkyl radical with 7 to about 12C-atoms, n is a whole number of 2 toinclusively 12 and the polymethylene chain (CH₂)_(n) can be interruptedby up to 5 ether, thioether, phenyl- or naphthyl groups; these areavailable as pharmaceutically suitable salts. Additional substitutedguanidines are: N'-(4-chlorobenzyl)-N⁵ -(2,4-dichlorobenzyl) biguanide;p-chlorobenzyl biguanide, 4-chlorobenzhydryl guanylurea;N-3-lauroxypropyl-N⁵ -p-chlorobenzyl biguanide;5,6-dichloro-2-guanidobenzimidazole; and N-p-chlorophenyl-N⁵-laurylbiguanide.

The long chain tertiary amines also possess antibacterial and antiplaqueactivity. Such antibacterial agents include tertiary amines having onefatty alkyl group (typically 12 to 18 carbon atoms) and 2poly(oxyethylene) groups attached to the nitrogen (typically containinga total of from 2 to 50 ethenoxy groups per molecule) and salts thereofwith acids and compounds of the structure: ##STR2## where R is a fattyalkyl group containing 12 to 18 carbon atoms and x, y and z total 3 orhigher, as well as salts thereof. Generally, cationic agents arepreferred for their antiplaque effectiveness.

The antibacterial antiplaque compound is preferably one which has aantibacterial activity such that its phenol coefficient is well over 50,more preferably well above 100, such as above about 200 or more for S.aureus; for instance the phenol coefficient (A.O.A.C.) of benzethoniumchloride is given by the manufacturer as 410, for S. aureus. Thecationic antibacterial agent will generally be a monomeric (or possiblydimeric) material molecular weight well below 2,000, such as less thanabout 1,000. It is, however, within the broader scope of the inventionto employ a polymeric cationic antibacterial agent. The cationicantibacterial is preferably supplied in the form of an orally acceptablesalt thereof, such as the chloride, bromide, sulfate, alkyl sulfonatesuch as methyl sulfonate and ethyl sulfonate, phenylsulfonate, such asp-methylphenyl sulfonate, nitrate, acetate, gluconate, etc.

The cationic antibacterial agents and long chain tertiary amineantibacterial agents effectively promote oral hygiene, particularly byremoving plaque. However, their use has been observed to lead tostaining of dental surfaces or discoloration.

The reason for the formation of such dental stain has not been clearlyestablished. However, human dental enamel contains a high proportion(about 95%) of hydroxyapatite which includes Ca⁺² and PO₄ ⁻³ ions. Inthe absence of denal plaque additional Ca⁺² and PO₄ ⁻³, particularlyfrom saliva, can be deposited on the enamel and such deposits caninclude color bodies which ultimately stain the tooth enamel as acalcified deposit thereon. It can be that as the cationic or long chaintertiary amine antibacterial agents remove plaque they also denatureprotein from saliva in the oral environment and the denatured proteincan then act as a nucleating agent which is deposited on and stains ordiscolors tooth enamel.

Previously employed additives which reduced dental staining by cationicantibacterial antiplaque agents also generally reduced the activity ofthe antibacterial agents or its ability to act on dental plaque tomeasurable degrees. Further Victamide (also known as Victamine C) whichis the condensation product of ammonia with phosphorus pentoxideactually increases staining even in the absence of a cationicantibacterial antiplaque agent and it and other known phosphoruscontaining agents such as disodium-ethane-1-hydroxy-1,1-diphosphonicacid salt precipitate in the presence of antibacterial agent such asbisbiguanido compound, thereby reducing the antiplaque effectiveness ofthe antibacterial agent.

It is an advantage of this invention that an antinucleating additive isprovided which prevents staining of dental enamel without substantiallyadversely affecting antibacterial and antiplaque activity of a cationicor long chain tertial amine antibacterial agent. Other advantages willbe apparent from consideration of the following disclosure.

In accordance with certain of its aspects this invention relates to anoral composition comprising an oral vehicle, a cationic or long chaintertiary amine antibacterial antiplaque agent and a water solublephosphono-containing compound of the formula: ##STR3## wherein R¹ ishydrogen, C₁ to C₄ alkyl or (CH₂)₁₂ COOH; and R² ##STR4## and mixturesthereof, and preferably of the formula: ##STR5## wherein R² is ##STR6##and mixtures thereof, or an orally acceptable salt thereof such asalkali metal (e.g. sodium and potassium), ammonium, C₁ -C₁₈ mono-,di-and tri-substituted ammonium (e.g. alkanol substituted such as mono-,di-and tri-ethanolammonium) salts.

Illustrative operative phosphonocarboxylic acids of formula (A) aboveinclude:

(a) 1-phosphonoethane-1,2-dicarboxylic acid;

(b) 2-phosphonopropane-2,3-dicarboxylic acid;

(c) 2-phosphonobutane-2,3-dicarboxylic acid;

(d) 1-phosphonopropane-1,2-dicarboxylic acid;

(e) 1-phosphonopropane-1,2,3-tricarboxylic acid;

(f) 1-phosphonobutane-2,3,4-tricarboxylic acid;

(g) 2-phosphonobutane-2,3,4-tricarboxylic acid;

(h) 1-phosphonobutane-1,2,3-tricarboxylic acid;

(i) 2-phosphonopentane-2,3,4-tricarboxylic acid;

(j) 1,1-diphosphonopropane-2,3-dicarboxylic acid;

(k) 1,1-diphosphonobutane-2,3-dicarboxylic acid;

(l) 2,2-diphosphonobutane-3,4-dicarboxylic acid; and

(m) 1,1-diphosphono-2-methylpropane-2,3-dicarboxylic acid.

Compounds (a) and (j) above are preferred.

Antibacterial agents which are cationic or long chain amine germicideswhich may be employed in the practice of this invention are describedabove. They are typically employed in amounts such that the oral productcontains between about 0.001% and 15% by weight of the agent. Preferablyfor desired levels of antiplaque effect, the finished oral productcontains about 0.01 to about 5%, and most preferably about 0.025% to1.0% by weight of the agent. These amounts refer to the quantity of thefree base form of the agent.

The stain which generally occurs on dental enamel is unexpectedlyprevented when the above-defined phosphonocarboxylic acids orwater-soluble salts thereof, are employed. These materials areanti-nucleating agents. In themselves (even in the absence of cationicantiplaque antibacterial agents) they are effective to reduce formationof dental calculus without unduly decalcifying enamel. However, not allanti-nucleating agents are effective to prevent stain by cationicantibacterial agents. Victamide actually increases staining even in theabsence of an antibacterial antiplaque agent.

The phosphonocarboxylic acids and suitable salts thereof employed hereincan be prepared in any convenient manner, for example, according to theteachings of British Pat. No. 1,394,172. U.S. Pat. No. 3,934,002discloses combining bis-biguanide antiplaque agents with certainphosphono-containing anticalculus agents differing from the instantphosphonocarboxylates.

The concentration of these phosphonocarboxylates in oral compositionscan range widely, typically upward from about 0.01% by weight with noupper limit except as dictated by cost or incompatibility with thevehicle. Generally, concentrations from about 0.01% to about 10% byweight are utilized. Oral compositions which in the ordinary course ofusage could be accidentally ingested preferably contain lowerconcentrations of these phosphonocarboxylates. Thus, a mouthwash inaccordance with this invention preferably contains less than about 3% byweight of phosphonocarboxylate. Dentifrice compositions, topicalsolutions and prophylactic pastes, the latter to be administeredprofessionally, can contain about 0.01% to 10%, preferably about 0.1% to5%, by weight of the phosphonocarboxylate. Most desirably, thephosphonocarboxylate is present in a molar excess relative to the amountof antibacterial antiplaque agent (based on the free base thereof), inorder to best minimize or prevent staining.

In certain highly preferred forms of the invention the oral compositionmay be substantially liquid in character, such as a mouthwash or rinse.In such a preparation the vehicle is typically a water-alcohol mixture.Generally, the ratio of water to alcohol is in the range of from about1:1 to about 20:1 preferably from 3:1 to 20:1 and most preferably about17:3, by weight. The total amount of water alcohol mixture in this typeof preparation is typically in the range of from about 70% to about99.9% by weight of the preparation. The pH of such liquid and otherpreparations of the invention is generally in the range of from about4.5 to about 9 and typically from about 5.5 to 8. The pH is preferablyin the range of from about 6 to about 8.0. It is noteworthy that thecompositions of the invention may be applied orally at a pH below 5without substantially decalcifying dental enamel.

Such liquid oral preparations may also contain a surface active agentand/or a fluorine-providing compound.

In certain other desirable forms of this invention, the oral compositionmay be substantially solid or pasty in character, such as a toothpowder,a dental tablet, a toothpaste or dental cream. The vehicle of such solidor pasty oral preparations contains polishing material. Examples ofpolishing materials are water-insoluble sodium metaphosphate, potassiummetaphosphate, tricalcium phosphate, dihydrated calcium phosphaste,anhydrous dicalcium phosphate, calcium pyrophosphate, magnesiumorthophosphate, trimagnesium phosphate, calcium carbonate, alumina,hydrated alumina, aluminum silicate, zirconium silicates, silica,bentonite, and mixtures thereof. Preferred polishing materials includecrystalline silica having particle sizes of up to 5 microns, a meansparticle size of up to 1.1 microns, and a surface area of up to 50,000cm² /gm. silica gel, complex amorphorus alkali metal aluminosilicate andhydrated alumina.

Alumina, particularly the hydrated alumina sold by Alcoa as C333, whichhas an alumina content of 64.9% by weight, a silica content of 0.008%, aferric oxide content of 0.003%, and a moisture content of 0.37% at 110°C., and which has a specific gravity of 2.42 and a particle size suchthat 100% of the particles are less than 50 microns and 84% of theparticles are less than 20 microns, is particularly desirable.

When visually clear gels are employed, a polishing agent of colloidalsilica, such as those sold under the trademark SYLOID as Syloid 72 andSyloid 74 or under the trademark SANTOCEL as Santocel 100 and alkalimetal aluminosilicate complexes are particularly useful, since they haverefractive indices close to the refractive indices of gellingagent-liquid (including water and/or humectant) systems commonly used indentifrices.

Many of the so called "water-insoluble" polishing materials are anionicin character and also include small amounts of soluble material. Thus,insoluble sodium metaphosphate may be formed in any suitable manner, asillustrated by Thorpe's Dictionary of Applied Chemistry, Volume 9, 4thEdition, pp. 510-511. The forms of insoluble sodium metaphosphate knownas Madrell's salt and Kurrol's salt are further examples of suitablematerials. These metaphosphate salts exhibit a minute solubility inwater, and therefore are commonly referred to as insolublemetaphosphates. There is present therein a minor amount of solublephosphate material as impurities, usually a few percent such as up to 4%by weight. The amount of soluble phosphate material, which is believedto include a soluble sodium trimetaphosphate in the case of insolublesodium metaphosphate, may be reduced by washing with water if desired.The insoluble alkali metal metaphosphate is typically employed in powderform of a particle size such that no more than 1% of the material islarger than 37 microns.

The polishing material is generally present in amounts ranging fromabout 20% to about 99% by weight of the oral preparation. Preferably, itis present in amounts ranging from about 20% to about 75% in toothpaste,and from about 70% to about 99% in toothpowder.

In the preparation of toothpowders, it is usually sufficient to admixmechanically, e.g., by milling, the various solid ingredients inappropriate quantities and particle sizes.

In pasty oral preparations the above-defined combination of theantibacterial antiplaque agent and phosphono-containing compound shouldbe compatible with the other components of the preparation. Thus, in atoothpaste, the liquid vehicle may comprise water and humectanttypically in an amount ranging from about 10% to about 90% by weight ofthe preparation. Glycerine, sorbitol, or polyethylene glycol may also bepresent as humectants or binders. Particularly advantageous liquidingredients comprise mixtures of water, glycerine and sorbitol.

In clear gels where the refractive index is an important consideration,about 3-30% by weight of water, 0 to about 80% by weight of glycerine,and about 20-80% by weight of sorbitol is preferably employed. A gellingagent, such as natural or synthetic gums or gum-like materials,typically Irish moss, sodium carboxymethylcellulose, methyl cellulose,or hydroxyethyl cellulose, may be employed. Other gelling agents whichmay be employed include gum tragacanth, polyvinylpyrrolidone and starch.They are usually present in toothpaste in an amount up to 10% by weight,preferably in the range of from about 0.5% to about 5%. The preferredgelling agents are methyl cellulose and hydroxyethyl cellulose. In atoothpaste or gel, the liquids and solids are proportioned to form acreamy or gelled mass which is extrudable from a pressurized containeror from a collapsible, e.g., aluminum or lead, tube.

The solid or pasty oral preparation which typically has a pH measured ona 20% slurry of about 4.5 to about 9, generally about 5.5 to about 8 andpreferably about 6 to about 8.0, may also contain a surface active agentand/or a fluorine-providing compound.

It will be understood that, as is conventional, the oral preparationsare to be sold or otherwise distributed in suitably labelled packages.Thus a jar of mouthrinse will have a label describing it, in substance,as a mouthrinse or mouthwash and having directions for its use; and atoothpaste will usually be in a collapsible tube, typically aluminum orlined lead, or other squeeze dispenser for metering out the contents,having a label describing it, in substance, as a toothpaste or dentalcream.

In oral compositions such as mouthrinses and toothpastes, a surfactantis often present, e.g. to promote foaming. It will be understood that itis preferable to employ nonionic surfactants rather than their anioniccounterparts. Examples of water-soluble nonionic surfactants arecondensation products of ethyleneoxide with various compounds reactivetherewith having long hydrophobic chains (e.g. aliphatic chains of 12 to20 carbon atoms) which condensation products ("ethoxamers") havehydrophilic polyoxyethylene moieties, such as condensation products ofethylene oxide and fatty acids, fatty alcohols, fatty amides, includingalcohols such as sorbitan monostearate or polypropyleneoxide (that isPluronic materials).

In certain forms of this invention a fluorine-providing compound ispresent in the oral preparation. These compounds may be slightly solublein water or may be fully water-soluble. They are characterized by theirability to release fluoride ions in water and by substantial freedomfrom reaction with other compounds of the oral preparation. Among thesematerials are inorganic fluoride salts, such as soluble alkali metal,alkaline earth metal and heavy metal salts, for example, sodiumfluoride, potassium fluoride, ammonium fluoride, lead fluoride, a copperfluoride such as cuprous fluoride, zinc fluoride, a tin fluoride such asstannic fluoride or stannous chlorofluoride, barium fluoride, sodiumfluorosilicate, ammonium fluorosilicate, sodium fluorozirconate, sodiummonofluorophosphate, aluminum mono- and di-fluorophosphate, andfluorinated sodium calcium pyrophosphate. Alkali metal and tinfluorides, such as sodium and stannous fluorides, sodiummonofluorophosphate and mixtures thereof, are preferred.

The amount of the fluorine-providing compound is dependent to someextent upon the type of compound, its solubility, and the type of oralpreparation, but it must be a nontoxic amount. In a solid oralpreparation, such as a toothpaste or toothpowder, an amount of suchcompound which releases a maximum of 1% by weight of the preparation isconsidered satisfactory. Any suitable minimum amount of such compoundmay be used, but it is preferable to employ sufficient compound torelease from 0.005% to 1%, and preferably about 0.1% of fluoride ion.Typically, in the cases of alkali metal fluorides and stannous fluoride,this component is present in an amount up to 2% by weight, based on theweight of the preparation, and preferably in the range of from 0.05% to1%. In the case of sodium monofluorophosphate, the compound may bepresent in an amount up to 7.6% by weight, more typically 0.76%.

In a liquid oral preparation such as a mouthwash, the fluorine-providingcompound is typically present in an amount sufficient to release up to0.13%, preferably from 0.0013% to 0.1% and most preferably from 0.0013%to 0.05%, by weight, of fluoride ion.

Various other materials may be incorporated in the oral preparations ofthis invention. Examples are whitening agents, preservatives, silicones,chlorophyll compounds, and ammoniated material such as urea, diammoniumphosphate, and mixtures thereof. These adjuvants, where present, areincorporated in the preparations in amounts which do not substantiallyadversely affect the properties and characteristics desired.

Any suitable flavoring or sweetening material may also be employed.Examples of suitable flavoring constituents are flavoring oils, e.g.,oils of spearmint, peppermint, wintergreen, sassafras, clove, sage,eucalyptus, marjoram, cinnamon, lemon, and orange, and methylsalicylate. Suitable sweetening agents include sucrose, lactose,maltose, sorbitol, sodium cyclamate, perillartine, and saccharine.Suitably, flavor and sweetening agents may together comprise from 0.01%to 5% or more of the preparation.

In preparing the oral compositions of this invention comprising theabove-defined combination of antibacterial agent andphosphono-containing compound in an oral vehicle which typicallyincludes water, it is highly preferred if not essential to add thephosphono-containing compound after the other ingredients (exceptperhaps some of the water) are mixed or contacted with each other toavoid a tendency for said agent to be precipitated.

For instance, a mouthrinse or mouthwash may be prepared by mixingethanol and water with flavoring oil, nonionic surfactant, humectant,cationic antibacterial antiplaque agent, such as benzethonium chlorideor chlorhexidine, sweetener, color and then the above-definedphosphono-containing compound, followed by additional water as desired.

A toothpaste may be prepared by forming a gel with humectant, gum orthickener such as hydroxyethyl cellulose, sweetener and adding theretopolishing agent, flavor, antibacterial agent, such as benzethoniumchloride or chlorhexidine, additional water, and then the above-definedphosphono-containing compound. If sodium carboxymethyl cellulose isemployed as the gelling agent the procedure of either U.S. Pat. No.3,842,168 or U.S. Pat. No. 3,843,779, modified by the inclusion of thephosphono-containing compound is followed.

In the practice of this invention an oral composition according to thisinvention, such as a mouthwash or toothpaste containing cationic or longchain amine antibacterial antiplaque agent in an amount effective topromote oral hygiene and the defined phosphono-containing compound in anamount effective to reduce staining of dental surfaces otherwiseresulting from the presence of the antibacterial antiplaque agent, isapplied regularly to dental enamel, preferably from about 5 times perweek to about 3 times daily, at a pH of about 4.5 to about 9, generallyabout 5.5 to about 8, preferably about 6 to 8.

The following specific examples are further illustrative of the natureof the present invention, but it is understood that the invention is notlimited thereto. The compositions are prepared in the usual manner andall amounts and proportions referred to herein and in the appendedclaims are by weight unless otherwise indicated.

EXAMPLES 1-25

In the following examples, a basic mouthwash formulation is prepared andtested as follows:

    ______________________________________                                        Mouthwash Formulation     Parts                                               ______________________________________                                        Flavored alcohol           15                                                 Pluronic F108 (polyalkene oxide                                                                         3                                                    block polymer)                                                               Glycerine                 10                                                  Benzethonium chloride (BC)                                                                              0.075                                               Sodium saccharin          0.03                                                Phosphono-containing compound                                                                           x                                                   Water q.s. to             100                                                 ph 7.0 (adjusted with 5N NaOH)                                                Appearance, stability     clear                                               ______________________________________                                    

The phosphono-containing compound, and about 10 parts of the water, areadded to the other previously mixed ingredients. Tooth stainingcharacteristics are tested by slurrying hydroxyapatite (Biogel) withsalivary protein and acetaldehyde and a pH7 phosphate buffer. Themixture is shaken at 37° C. until a light brown color is formed, whichcolored material is separated. Color levels are determined on a GardnerColor Difference Meter before and after the test composition is appliedto the colored material.

The following Table I shows the antistain results when the indicatedamounts (x) of the indicated phosphono-containing compound are employedin the above Mouthwash Formulation.

                  TABLE I                                                         ______________________________________                                        ANTISTAIN                                                                           Phosphono  Parts              Reflectance                               Ex.   Compound   (x)      Reflectance                                                                             Difference                                ______________________________________                                        1     --         0        40.0      0                                         2     DPPD*      0.1      45.0      5.0                                       3     "          0.2      49.0      7.0                                       4     "          0.3      53.0      13.0                                      5     "          0.4      60.0      20.0                                      6     "          0.5      53.0      13.0                                      7     "          1.0      56.0      16.0                                      8     PEDA**     0.1      43.0      3.0                                       9     "          0.2      54.0      14.0                                      10    "          0.3      58.0      18.0                                      11    "          0.4      52.0      12.0                                      12    "          0.5      54.0      14.0                                      13    "          0.6      60.0      20.0                                      14    "          1.0      51.0      11.0                                      ______________________________________                                         *1,1-diphosphonopropane-2,3-dicarboxylic acid.                                **1-phosphonoethane-1,2-dicarboxylic acid.                               

The above results plainly establish that the phosphonoalkanepolycarboxylic acid additives of the present invention, as exemplifiedby DPPD and PEDA, substantially reduce dental staining ordinarilyproduced by BC. These tests are conducted with the pH of the formulationadjusted to about 7.0, the pH prior to adjustment ranging from about 3.5to 5.0. Formulations adjusted to pH ranging from about 5 to 8 yieldsimilar results.

Substitution of equivalent amounts of the following phosphono-containingcompounds for those employed in Examples 1-14 yield formulations alsoproducing unexpected reductions in dental staining:

    ______________________________________                                        Example   Phosphono-Containing Compound                                       ______________________________________                                        15        2-phosphonopropane-2,3-dicarboxylic acid                            16        2-phosphonobutane-2,3-dicarboxylic acid                             17        1,1-diphosphonobutane-2,3-dicarboxylic acid                         18        1-phosphonopropane-1,2,3-tricarboxylic                                         acid                                                               19        2-phosphonobutane-2,3,4-tricarboxylic acid                          ______________________________________                                    

Substitution of equivalent amounts of the following antibacterialantiplaque agents for the BC employed in Examples 1-19 yieldformulations also producing unexpected reductions in in dental staining:

    ______________________________________                                        Example   Antibacterial Antiplaque Agent                                      ______________________________________                                        20        chlorhexidine diacetate                                             21        chlorhexidine digluconate                                           22        dodecyl trimethyl ammonium bromide                                  23        cetyl pyridinium chloride                                           24                                                                                       ##STR7##                                                           25        alexidine dihydrochloride                                           ______________________________________                                    

It is further notable that the in vitro antiplaque activity of theabove-exemplified formulations containing the indicatedphosphono-containing additive compounds are substantially equal tocorresponding formulations omitting such compounds.

EXAMPLE 26

In vivo tests for antiplaque and antistain activity are conducted onbeagles with the mouthwash formulation of Example 6 containing 0.075parts of BC and 0.5 parts of DPPD, the control formulation of Example 1containing 0.075 parts of BC and no DPPD, and a placebo devoid of bothBC and DPPD. The beagles are first subjected to dental prophylaxis toremove existing soft and hard dental deposits. A disclosing solution isused to insure complete removal. Applications are made by gentlespraying twice a day, 5 days a week for 6 weeks. Stain is evaluatedrelatively by visual observation of the oral cavity. Plaque is evaluatedafter spraying the teeth with disclosing solution. The results are asfollows:

    ______________________________________                                                                          Stain                                                 No.   Mean              Difference                                            of    Plaque   Mean     Compared to                                           Dogs  Score    Stain    Placebo                                     ______________________________________                                        Placebo     8       2.4     0.38    0                                         Control (+BC)                                                                             7       1.8     0.53    +39.4%                                    +BC+DPPD+   8       1.8     0.32    -42.3%                                    ______________________________________                                    

It is clear from the above results that the phosphono-containingadditive compounds of this invention, as exemplified by DPPD,significantly and substantially reduce dental staining (by 42.3%) causedby antibacterial antiplaque agents as exemplified by the cationic BC, infact reducing staining to less than the placebo. These results also showthat such additive compounds do not affect the antiplaque activity ofthe stain-producing antibacterial antiplaque agents.

EXAMPLES 27, 28

The following formulations exemplify toothpastes with antiplaqueactivity and reduced staining:

    ______________________________________                                                             Example                                                                       (Parts)                                                                       27    28                                                 ______________________________________                                        Hydrated alumina       30      30                                             Glycerine              16      16                                             Sorbitol (70%)         6       6                                              Pluronic F-108         3       3                                              Hydroxyethyl cellulose 1.2     1.2                                            Benzethonium chloride  0.5     --                                             Chlorhexidine digluconate (20%)                                                                      --      4.725                                          DPPD                   2       2                                              Sodium saccharin       0.17    0.17                                           Flavor                 0.8     0.8                                            Water q.s. to          100     100                                            ______________________________________                                    

This invention has been described with respect to preferred embodimentsand it will be understood that modifications and variations thereofobvious to those skilled in the art are to be included within the spiritand purview of this application and the scope of the appended claims.

What is claimed is:
 1. An oral composition comprising an oral vehicle,at least one nitrogen containing antibacterial antiplaque agent selectedfrom the group consisting of cationic bis-guanido and quaternaryammonium antibacterial antiplaque agents and at least one water solublephosphoncarboxylate compound of the formula: ##STR8## wherein R¹ ishydrogen, C₁ to C₄ alkyl or (CH₂)₁₋₂ COOX; and R² ##STR9## and X is anorally acceptable cation.
 2. The oral composition of claim 1 whereinsaid antibacterial antiplaque agent is present in amount to provideabout 0.001% to about 15% by weight based on the free base form of saidagent and said phosphonocarboxylate compound is present in amount ofabout 0.01% to about 10% by weight.
 3. The oral composition of claim 2wherein said antibacterial antiplaque agent is present in amount ofabout 0.01% to about 5% by weight based on the free base form of saidagent and said phosphonocarboxylate is present in a molar excessrelative to said agent.
 4. The oral composition of claim 2 wherein saidantibacterial antiplaque agent is a bis-guanido antiplaque agent.
 5. Theoral composition of claim 4 wherein said antibacterial antiplaque agentis a pharmaceutically acceptable water soluble salt of an agent selectedfrom the group consisting of chlorhexidine and alexidine.
 6. The oralcomposition of claim 5 wherein said antibacterial antiplaque agent ispharmaceutically acceptable water soluble salt of chlorhexidine.
 7. Theoral composition of claim 2 wherein said antibacterial antiplaque agentis benzethonium chloride.
 8. The oral composition of claim 2 whereinsaid antibacterial antiplaque agent is a quaternary ammonium compoundcontaining 1 to 2 alkyl groups of 8 to 20 carbon atoms.
 9. The oralcomposition of claim 8 wherein said antibacterial antiplaque agent iscetyl pyridinium chloride.
 10. The oral composition of claim 2 whereinthe phosphonocarboxylate is 1,1-diphosphonopropane-2,3-dicarboxylic acidor 1-phosphonoethane-1,2-dicarboxylic acid or an orally acceptable saltthereof.
 11. The oral composition of claim 1 wherein said vehicle is anaqueous-alcohol and said composition is a mouthwash of pH of about 4.5to about
 9. 12. The oral composition of claim 1 wherein said vehiclecomprises a liquid vehicle and a gelling agent and a dentally acceptablepolishing material is present and said composition is a toothpaste of pHof about 4.5 to about
 9. 13. The mouthwash composition of claim 11containing about 0.01% to about 5.0% based on its free base weight ofbenzethonium chloride and relative thereto, a molar excess within therange of about 0.1% to about 5% by weight of said phosphonocarboxylatecompound.
 14. The mouthwash composition of claim 11 containing about0.01% to about 5% based on its free base weight of a water-solublepharmaceutically acceptable salt of chlorhexidine and, relative thereto,a molar excess within the range of about 0.1% to about 5% by weight ofsaid phosphonocarboxylate compound.
 15. A method of improving oralhygiene comprising applying to the oral cavity an effective amount of anoral composition as defined in claim 1.